Helicobacter pylori is a major human pathogen for which increasing antibiotic resistance constitutes a serious threat to human health. Molecular mechanisms underlying this resistance have been ...intensively studied and are discussed in this Review. Three profiles of resistance - single drug resistance, multidrug resistance and heteroresistance - seem to occur, probably with overlapping fundamental mechanisms and clinical implications. The mechanisms that have been most studied are related to mutational changes encoded chromosomally and disrupt the cellular activity of antibiotics through target-mediated mechanisms. Other biological attributes driving drug resistance in H. pylori have been less explored and this could imply more complex physiological changes (such as impaired regulation of drug uptake and/or efflux, or biofilm and coccoid formation) that remain largely elusive. Resistance-related attributes deployed by the pathogen cause treatment failures, diagnostic difficulties and ambiguity in clinical interpretation of therapeutic outcomes. Subsequent to the increasing antibiotic resistance, a substantial drop in H. pylori treatment efficacy has been noted globally. In the absence of an efficient vaccine, enhanced efforts are needed for setting new treatment strategies and for a better understanding of the emergence and spread of drug-resistant bacteria, as well as for improving diagnostic tools that can help optimize current antimicrobial regimens.
The unique genetic makeup and remarkable competency of Vibrio cholerae are the key factors that help the cholera pathogen adapt rapidly to adverse environmental conditions and resist the detrimental ...effect of antimicrobial agents. In the last few decades, V. cholerae that causes acute watery diarrhoeal disease cholera has emerged as a notorious multidrug resistant (MDR) enteric pathogen. Although chromosomal mutations can contribute to antimicrobial resistance (AMR), the frequent acquisition of extrachromosomal mobile genetic elements (MGEs) from closely/distantly related bacterial species are major players in V. cholerae drug resistance. Whole genome sequence analysis of clinical and environmental V. cholerae strains revealed that the genome of most of the recent isolates harbour integrating conjugative elements (ICEs), plasmids, superintegron, transposable elements and insertion sequences, which are the key carriers of genetic traits encoding antimicrobial resistance function. Different antimicrobial resistance genes identified in V. cholerae can contribute in antibiotic resistance by facilitating one of the following three mechanisms; (i) reduced permeability or active efflux of the antibiotics, (ii) alteration of the antibiotic targets by introducing post-transcriptional/translational modifications and (iii) hydrolysis or chemical modification of antibiotics. Here, we present an overview of the present insights on the emergence and mechanisms of AMR in V. cholerae.
White flight Kruse, Kevin M
2013., 20130711, 2013, 2005, 2007, 2007-08-14, Letnik:
50
eBook
During the civil rights era, Atlanta thought of itself as "The City Too Busy to Hate," a rare place in the South where the races lived and thrived together. Over the course of the 1960s and 1970s, ...however, so many whites fled the city for the suburbs that Atlanta earned a new nickname: "The City Too Busy Moving to Hate."
In this reappraisal of racial politics in modern America, Kevin Kruse explains the causes and consequences of "white flight" in Atlanta and elsewhere. Seeking to understand segregationists on their own terms,White Flightmoves past simple stereotypes to explore the meaning of white resistance. In the end, Kruse finds that segregationist resistance, which failed to stop the civil rights movement, nevertheless managed to preserve the world of segregation and even perfect it in subtler and stronger forms.
Challenging the conventional wisdom that white flight meant nothing more than a literal movement of whites to the suburbs, this book argues that it represented a more important transformation in the political ideology of those involved. In a provocative revision of postwar American history, Kruse demonstrates that traditional elements of modern conservatism, such as hostility to the federal government and faith in free enterprise, underwent important transformations during the postwar struggle over segregation. Likewise, white resistance gave birth to several new conservative causes, like the tax revolt, tuition vouchers, and privatization of public services. Tracing the journey of southern conservatives from white supremacy to white suburbia, Kruse locates the origins of modern American politics.
Some images inside the book are unavailable due to digital copyright restrictions.
Infections arising from multidrug-resistant pathogenic bacteria are spreading rapidly throughout the world and threaten to become untreatable. The origins of resistance are numerous and complex, but ...one underlying factor is the capacity of bacteria to rapidly export drugs through the intrinsic activity of efflux pumps. In this Review, we describe recent advances that have increased our understanding of the structures and molecular mechanisms of multidrug efflux pumps in bacteria. Clinical and laboratory data indicate that efflux pumps function not only in the drug extrusion process but also in virulence and the adaptive responses that contribute to antimicrobial resistance during infection. The emerging picture of the structure, function and regulation of efflux pumps suggests opportunities for countering their activities.
Waste water and waste water treatment plants can act as reservoirs and environmental suppliers of antibiotic resistance. They have also been proposed to be hotspots for horizontal gene transfer, ...enabling the spread of antibiotic resistance genes between different bacterial species. Waste water contains antibiotics, disinfectants, and metals which can form a selection pressure for antibiotic resistance, even in low concentrations. Our knowledge of antibiotic resistance in waste water has increased tremendously in the past few years with advances in the molecular methods available. However, there are still some gaps in our knowledge on the subject, such as how active is horizontal gene transfer in waste water and what is the role of the waste water treatment plant in the environmental resistome? The purpose of this review is to briefly describe some of the main methods for studying antibiotic resistance in waste waters and the latest research and main knowledge gaps on the issue. In addition, some future research directions are proposed.
Waste water and waste water treatment plants are potential hot spots of selection of antibiotic resistance and horizontal gene transfer.
Hospitals are only a small proportion of the sources of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic-resistance genes (ARGs); municipal wastes are also vital sources.
Mobile genetic elements are likely to play a role in the dissemination of antibiotic resistance in waste water.
The detection of an ARG does not mean that this is conferring resistance in the host. Thus, molecular methods are needed that can distinguish between ARG carriage in the host chromosome and ARG which confers resistance or a risk to the treatment of pathogens.
Waste waters contain traces of antibiotics and other compounds which can cause a selection pressure for antibiotic resistance, and even low concentrations are able to cause selection pressure.
Cancer is one of the main causes of death worldwide. Despite the significant development of methods of cancer healing during the past decades, chemotherapy still remains the main method for cancer ...treatment. Depending on the mechanism of action, commonly used chemotherapeutic agents can be divided into several classes (antimetabolites, alkylating agents, mitotic spindle inhibitors, topoisomerase inhibitors, and others). Multidrug resistance (MDR) is responsible for over 90% of deaths in cancer patients receiving traditional chemotherapeutics or novel targeted drugs. The mechanisms of MDR include elevated metabolism of xenobiotics, enhanced efflux of drugs, growth factors, increased DNA repair capacity, and genetic factors (gene mutations, amplifications, and epigenetic alterations). Rapidly increasing numbers of biomedical studies are focused on designing chemotherapeutics that are able to evade or reverse MDR. The aim of this review is not only to demonstrate the latest data on the mechanisms of cellular resistance to anticancer agents currently used in clinical treatment but also to present the mechanisms of action of novel potential antitumor drugs which have been designed to overcome these resistance mechanisms. Better understanding of the mechanisms of MDR and targets of novel chemotherapy agents should provide guidance for future research concerning new effective strategies in cancer treatment.
can be present as a cutaneous, mucosal or deep-seated organ infection, which is caused by more than 20 types of
sp., with
being the most common. These are pathogenic yeast and are usually present in ...the normal microbiome. High-risk individuals are patients of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), organ transplant, and diabetes. During infection, pathogens can adhere to complement receptors and various extracellular matrix proteins in the oral and vaginal cavity. Oral and vaginal
results from the overgrowth of
sp. in the hosts, causing penetration of the oral and vaginal tissues. Symptoms include white patches in the mouth, tongue, throat, and itchiness or burning of genitalia. Diagnosis involves visual examination, microscopic analysis, or culturing. These infections are treated with a variety of antifungals that target different biosynthetic pathways of the pathogen. For example, echinochandins target cell wall biosynthesis, while allylamines, azoles, and morpholines target ergosterol biosynthesis, and 5-Flucytosine (5FC) targets nucleic acid biosynthesis. Azoles are commonly used in therapeutics, however, because of its fungistatic nature,
sp. evolve azole resistance. Besides azoles,
sp. also acquire resistance to polyenes, echinochandins, and 5FC. This review discusses, in detail, the drug resistance mechanisms adapted by
sp.
Infections caused by multidrug resistant bacteria represent a therapeutic challenge both in clinical settings and in livestock production, but the prevalence of antibiotic resistance genes among the ...species of bacteria that colonize the gastrointestinal tract of ruminants is not well characterized. Here, we investigate the resistome of 435 ruminal microbial genomes in silico and confirm representative phenotypes in vitro. We find a high abundance of genes encoding tetracycline resistance and evidence that the tet(W) gene is under positive selective pressure. Our findings reveal that tet(W) is located in a novel integrative and conjugative element in several ruminal bacterial genomes. Analyses of rumen microbial metatranscriptomes confirm the expression of the most abundant antibiotic resistance genes. Our data provide insight into antibiotic resistange gene profiles of the main species of ruminal bacteria and reveal the potential role of mobile genetic elements in shaping the resistome of the rumen microbiome, with implications for human and animal health.
Poor microbial water quality jeopardizes the health and safety of food produced by aquaculture farms. Three fish farms and transect sites in Singapore were assessed for microbial water quality and ...antimicrobial resistance determinants. Of the 33 multidrug resistant E. coli isolated from surface waters of the Johor Straits, 81.8% were ESBL producers. The relative abundance of sul1, qnrA and intI1 genes were higher in sediments than surface waters. Among the surface water samples, higher concentrations (10−1−101) of beta-lactamases (blaSHV, blaOXA, blaCTX-M) were detected in the transect sites. This study highlights a potential antimicrobial resistance transmission chain from environmental waters, to animal carriers and humans.
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•Non-toxigenic Vibrio spp. were detected in samples.•No significant differences in the abundance of indicator bacteria in fish farms and transects•Fish farms had higher percentage of resistant E. coli.•IntI1, sul1 and qnrA abundance was higher in fish farm sediments than waters.•Possible sources of contamination from surrounding environment
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